Sodium Bicarbonate for the Treatment of Severe Metabolic Acidosis With Moderate or Severe Acute Kidney Injury in ICU

NCT04010630 | Completed DMC

• 1 other identifier: 7754
• Study Type: interventional
• Target: 640
• Locations: 1 country
• Sites: 1

Brief Summary

Severe metabolic acidemia in the critically ill (pH equal or less than 7.20; PaCO2 equal or less than 45mmHg and bicarbonate concentration equal or less than of 20 mmol/l) is associated with a 50% rate of day 28 mortality. Moderate to severe acute kidney injury is a frequent cause of metabolic acidemia in the critically ill. When both severe metabolic acidemia and moderate to severe acute kidney injury are observed, day 28 mortality is approximatively 55-60%. Severe acidemia has been shown to be a biomarker of severity but may also contribute by itself to outcome. Investigators recently performed a multiple center randomised clinical trial (BICARICU-1) that suggests that sodium bicarbonate infusion titrated to maintain the pH equal or more than 7.30 is associated with a higher survival rate (secondary endpoint) in patients presenting both severe metabolic acidemia and moderate to severe acute kidney injury patients. Whether sodium bicarbonate infusion may improve long term survival (Day 90, primary outcome) in these severe acute kidney injury patients is currently unknown.

Conditions

Metabolic Acidosis; Acute Kidney Injury

Outcome Measures

Primary Outcomes (1)

• Day 90 all-cause mortality

  Day 90 all cause mortality

  Day 90

Secondary Outcomes (11)

• Organ Failure

  up to 7 days after enrolment

• Overall fluid balance and solutions intake

  Day 2

• Electrolytes adverse events during the ICU stay

  ICU discharge or Day 28

• Organ Support Day 90 alive free days

  Day 90

• Hospital acquired infections

  ICU discharge or Day 28

Study Arms (2)

control group

NO INTERVENTION

The physicians will resuscitate the patients according to the current critical care medicine guidelines.

Sodium bicarbonate group

EXPERIMENTAL

Patients randomly assigned to bicarbonate group will receive intravenous 4.2% sodium bicarbonate titrated from 125ml to 250ml in 30min at physician's discretion to target a pH equal or above 7.30. Bicarbonate infusion will be repeated up to 1000ml per 24h. Arterial blood gases will be repeated from 3 to 6 times during the first 24h at physician's discretion

Drug: Sodium bicarbonate infusion

Interventions

Sodium bicarbonate infusion DRUG

Patients randomly assigned to bicarbonate group will receive intravenous 4.2% sodium bicarbonate titrated from 125ml to 250ml in 30min at physician's discretion to target a pH equal or above 7.30. Bicarbonate infusion will be repeated up to 1000ml per 24h. Arterial blood gases will be repeated from 3 to 6 times during the first 24h at physician's discretion. Bicarbonate infusion recommendations will be as follow: a central line is recommended, infusion will be slow (125-250ml in 30 min, no intravenous push), careful surveillance of metabolic alkalosis, cardiogenic pulmonary edema, kalemia, natremia and calcemia. Repeated arterial blood gases will be suggested to monitor these critically ill patients and physicians will be reinformed of the potential side effects of sodium bicarbonate infusion.

Sodium bicarbonate group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged from 18 years old
• Admitted in the ICU where the BICARICU-2 trial takes place
• Within 6h before enrolment, the patient MUST present on the same arterial blood gas (the last available before enrollment) the 3 following criteria:
• pH ≤ 7.20 ; Bicarbonatemia ≤ 20 mmol/l ; AND PaCO2 ≤ 45mmHg ;
• Moderate to severe acute kidney injury ("Kidney Disease Improving Global Outcome", KDIGO group of 2 or 3)
• Within 48h of ICU admission, a total SOFA ≥ 4 OR an arterial lactate concentration ≥ 2 mmol/l
• Subjects must be covered by public health insurance

You may not qualify if:

• Pure respiratory acidosis (defined by pH 7.20, PaCO2 \>50 mmHg, bicarbonatemia equal or greater than (PaCO2-40)/10 + 24), digestive or urinary tract proven loss of fluid (equal or greater than 1500ml/24h) with concomitant loss of sodium bicarbonate, chronic kidney insufficiency (creatinine clearance ≤ 10ml/min), proven tubular acidosis, ketoacidosis, exogenous acids poisoning (aspirin, methanol, ), PaCO2 \> 45 mmHg and spontaneous breathing, sodium bicarbonate infusion or renal replacement therapy within 24h prior to screening prior to screening or imminent in the next 6h.
• Pregnant or breast feeding patient
• Patient who is in a dependency or employment with the sponsor or the investigator
• Life expectancy less than 48h
• Consent refusal from the patient or his/her next of kin and the impossibility to enrol using the emergency procedure
• Patients protected by law (Art.L 1121-5, 1121-6, 1121-8 du Code de la santé publique)
• Absence of a French Health Care Insurance coverage

Sponsors & Collaborators

• University Hospital, Montpellier: lead

Study Sites (1)

Service de médecine intensive et réanimation

Montpellier, 34000, France

Location

Related Publications (2)

• Jung B, Jabaudon M, De Jong A, Bitker L, Audard J, Klouche K, Sarton B, Guitton C, Lasocki S, Rieu B, Canet E, Jeantrelle C, Roquilly A, Mayaux J, Verdonk F, Pottecher J, Ferrandiere M, Riu B, Garcon P, Assefi M, Detouche P, Forel JM, Roger C, Bourenne J, Jacquier S, Bougon D, Rolle A, Corne P, Benchabane N, Richard JC, Asehnoune K, Chanques G, Reignier J, Belafia F, Fosset M, Huguet H, Futier E, Molinari N, Jaber S; BICARICU-2 Study Group. Sodium Bicarbonate for Severe Metabolic Acidemia and Acute Kidney Injury: The BICARICU-2 Randomized Clinical Trial. JAMA. 2025 Dec 9;334(22):2000-2010. doi: 10.1001/jama.2025.20231.

  PMID: 41159812 DERIVED

• Jung B, Huguet H, Molinari N, Jaber S. Sodium bicarbonate for the treatment of severe metabolic acidosis with moderate or severe acute kidney injury in the critically ill: protocol for a randomised clinical trial (BICARICU-2). BMJ Open. 2023 Aug 17;13(8):e073487. doi: 10.1136/bmjopen-2023-073487.

  PMID: 37591655 DERIVED

MeSH Terms

Conditions

Acidosis; Acute Kidney Injury

Condition Hierarchy (Ancestors)

Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2019
• First Posted: July 8, 2019
• Study Start: October 7, 2019
• Primary Completion: December 19, 2023
• Study Completion: June 17, 2024
• Last Updated: July 25, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share
• Time Frame: 12 months after the main publication
• Access Criteria: Data are provided to qualified investigators free of charge. Required documents to request data include a summary of the research plan, request form, and IRB review. Dataset will be shared after careful examination by the study board of investigators.

Locations

FR (1)